Microtubule-Based Control of Motor-Clutch System Mechanics in Glioma Cell Migration

Cell Reports
Louis S PrahlDavid J Odde

Abstract

Microtubule-targeting agents (MTAs) are widely used chemotherapy drugs capable of disrupting microtubule-dependent cellular functions, such as division and migration. We show that two clinically approved MTAs, paclitaxel and vinblastine, each suppress stiffness-sensitive migration and polarization characteristic of human glioma cells on compliant hydrogels. MTAs influence microtubule dynamics and cell traction forces by nearly opposite mechanisms, the latter of which can be explained by a combination of changes in myosin motor and adhesion clutch number. Our results support a microtubule-dependent signaling-based model for controlling traction forces through a motor-clutch mechanism, rather than microtubules directly relieving tension within F-actin and adhesions. Computational simulations of cell migration suggest that increasing protrusion number also impairs stiffness-sensitive migration, consistent with experimental MTA effects. These results provide a theoretical basis for the role of microtubules and mechanisms of MTAs in controlling cell migration.

Citations

May 28, 2019·Journal of Cellular Physiology·Qiang MaXiaolan Guo
May 9, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kayla J WolfSanjay Kumar
Apr 1, 2021·Molecular Biology of the Cell·Kirill LavrenyukKris Noel Dahl
Jun 9, 2021·Cell Metabolism·Stéphanie TorrinoThomas Bertero

Datasets Mentioned

BETA
PXD008939

Methods Mentioned

BETA
GTPase
fluorescence recovery after photobleaching
nucleotide exchange
transfection
protein assay
immunoprecipitation

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Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

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